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Thursday, 30 October 2008

Scientists identify machinery that helps make memoriesThursday, 30 October 2008
A major puzzle for neurobiologists is how the brain can modify one microscopic connection, or synapse, at a time in a brain cell and not affect the thousands of other connections nearby. Plasticity, the ability of the brain to precisely rearrange the connections between its nerve cells, is the framework for learning and forming memories.
Duke University Medical Center researchers have identified a missing-link molecule that helps to explain the process of plasticity and this could lead to targeted therapies.
The discovery of a molecule that moves new receptors to the synapse so that the neuron (nerve cell) can respond more strongly helps to explain several observations about plasticity, said Michael Ehlers, M.D., Ph.D., a Duke professor of neurobiology and senior author of the study published in the Oct. 31 issue of Cell.
"This may be a general delivery system in the brain and in other types of cells, and could have significance for all cell signalling."
Ehlers said this could be a general way for all cells to locally modify their membranes with receptors, a process critical for many activities – cell signalling, tumour formation and tissue development.
"Part of plasticity involves getting receptors to the synaptic connections of nerve cells," Ehlers said.
"The movement of neurotransmitter (chemical) receptors occurs through little packages that deliver molecules to the synapse when new memories form. What we have discovered is the molecular motor that moves these packages when synapses are active."
When neurons fire at the same time, their connections strengthen and a person can associate certain features.
"Once you have heard someone's name, seen his face, where he was standing, all these features can be bound into a unified packet of information – a percept – and at a very cellular level this occurs by strengthening synaptic connections between co-active neurons," said Ehlers, who is also a Howard Hughes Medical Investigator.
To learn and make new associations, the brain alters the strengths of the synapses' electrical inputs onto cells that compute these features. Scientists studied the hippocampus, where memories form, but this machinery could operate in other brain areas.
"One of earliest changes in Alzheimer's disease is synapse dysfunction, so this molecule might be a new target for that disease," he said.
"Abnormal movement of receptors may be implicated in brain development, in autism." He said the molecule potentially is involved "in the abnormal electrical activity of epilepsy and the overactive brain pathways of addiction."
In a series of biochemistry and microscopic imaging experiments, Ehlers and colleagues found that the myosin Vb (five-b) molecule in hippocampus neurons responded to a flow of calcium ions from the synaptic space by popping up and into action. One end of the myosin is attached the mesh-like actin filaments so it can "walk" to the end of the nerve cells where receptors are. On its other end, it tows an endosome, a packet that contains new receptors.
"These endosomes are like little memories waiting to happen," Ehlers said.
"They are reservoirs of neurotransmitter receptors that brain cells deploy to add more receptors to a particular synapse. More receptors equal stronger synapses."
Electrical impulses cause one nerve cell to dump its neurotransmitter, in this case, glutamate, into the small space between neurons (the synapse), which activates neurotransmitter receptors on the receiving side. These ion channels open in response to neurotransmitter and generate the electrical impulse.
When the scientists blocked myosin in single cells, this stopped the addition of new receptors and prevented electrical impulses from getting stronger, showing that myosin is essential to enhancing nerve cell connections.
"This is a very basic cellular mechanism of brain plasticity. It is likely fundamental to brain development and disease," Ehlers said.
"The myosin Vb molecule gives us a new way to think about designing therapies for treating memory loss, psychiatric disease and brain development."
Reference:
Myosin Vb Mobilizes Recycling Endosomes and AMPA Receptors for Postsynaptic Plasticity
Zhiping Wang, Jeffrey G. Edwards, Nathan Riley, D. William Provance, Ryan Karcher, Xiang-dong Li, Ian G. Davison, Mitsuo Ikebe, John A. Mercer, Julie A. Kauer and Michael D. Ehlers
Cell, Volume 135, Issue 3, 535-548, 31 October 2008
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ZenMaster

Study provides a practical step to advance progress in stem cell therapies
Thursday, 30 October 2008
New research from the University of Bristol brings stem cell therapies for heart disease one step closer. The findings reveal that our bodies' ability to respond to an internal 'mayday' signal may hold the key to success for long-awaited regenerative medicine.
Dr Nicolle Kränkel and colleagues at the Bristol Heart Institute have discovered how our bodies initiate DIY rescue and repair mechanisms when blood supply is inadequate, for example in diabetic limbs or in the heart muscle during heart attack. Their findings also provide a practical step to advance progress in stem cell therapies.
In healthy people, reduced oxygen supply can occur in certain situations, e.g. after an injury. The affected tissues release chemical messengers that 'call' to a type of circulating stem cells (EPCs) for help to re-establish blood supply via the growth of new blood vessels. A group of Bristol researchers have found that kinins, for long time considered inflammatory substances, are among the messengers supporting blood vessel growth.
In this study, published in Circulation Research, Dr Kränkel and colleagues found that EPCs respond to kinins by travelling to the target tissue and invading it to assist healing. In patients with angina, EPCs cannot respond to the distress call because they lack a kinin sensor (the 'kinin receptor') on their surface. The oxygen-starved tissue is therefore left with reduced blood supply.
In heart attack patients they saw that a proportion of the circulating EPCs were able to sense the kinin signal and respond.
Dr Kränkel, Research Associate at the Bristol Heart Institute, said:
"Our findings showed that heart attack patients possess the functional cells needed to repair blood supply to their heart, but they're hidden amongst a muddle of others."
The team purified the kinin-sensitive EPCs from the total stem cell population to create an enriched sample that has huge potential as a powerful regenerative therapy.
Dr Kränkel added:
"In previous clinical stem cell trials, a mixture of different types of cells was used. We've used kinin like a magnet to attract and extract the most effective repair cells from the mass of different types. This enriched sample should increase the therapeutic potential, especially in heart attack patients where quick and efficient treatment is crucial for long term outcome."
Professor Jeremy Pearson, Associate Medical Director of the British Heart Foundation – one of the study's funders – said:
"The team have made fascinating discoveries about our DIY repair systems and have translated them into practical use. They've intelligently employed the body's own strategies to develop a method that may take us a step closer to truly effective stem cell therapies for heart patients."
Reference:
Role of Kinin B2 Receptor Signaling in the Recruitment of Circulating Progenitor Cells With Neovascularization Potential
Nicolle Kränkel, Rajesh G. Katare, Mauro Siragusa, Luciola S. Barcelos, Paola Campagnolo, Giuseppe Mangialardi, Orazio Fortunato, Gaia Spinetti, Nguyen Tran, Kai Zacharowski, Wojciech Wojakowski, Iwona Mroz, Andrew Herman, Jocelyn E. Manning Fox, Patrick E. MacDonald, Joost P. Schanstra, Jean Loup Bascands, Raimondo Ascione, Gianni Angelini, Costanza Emanueli and Paolo Madeddu
Circulation Research, Oct 16, 2008, doi: 10.1161/CIRCRESAHA.108.179952.........
ZenMaster

Monday, 20 October 2008

H9N2 virus ‘core’ bird flu vaccine protects both people and petsMonday, 20 October 2008
A single vaccine could be used to protect chickens, cats and humans against deadly flu pandemics, according to an article published in the November issue of the Journal of General Virology. The vaccine protects birds and mammals against different flu strains and can even be given to birds while they are still in their eggs, allowing the mass vaccination of wild birds.
The emergence of bird flu has posed a major challenge to scientists designing vaccines as it can infect a number of different animals, including birds, pets and people. Now, researchers in the USA have discovered that a vaccine based on a bird flu virus could be used to protect several species against different influenza viruses.
"The world is experiencing a pandemic of influenza in birds caused by an H5N1 virus. Although it has been restricted to Eurasia and some countries in Africa, there is a risk that this virus may spread worldwide," said Professor Daniel Perez from the University of Maryland, USA.
"The H5N1 virus also has an unusual expanded host range: not only birds and humans have been infected but also cats, which are usually resistant to influenza. To prepare for a pandemic, it would be ideal to have a vaccine that could be used in multiple animal species."
The researchers found that the central genes or 'backbone' of the H9N2 virus that infects guinea fowl can protect birds and mice against highly pathogenic strains of influenza. They modified the virus to make it less pathogenic and then used it to vaccinate mice. Three weeks after being vaccinated, the mice were infected with the potentially lethal H1N1 virus – the same virus that caused the 1918 Spanish flu pandemic. All the vaccinated mice survived with no signs of disease. Vaccinated mice also survived infection with the deadly H5N1 bird flu virus, again showing no signs of disease.
"Our results show that the H9N2 backbone vaccine can be used to protect mice against two different, highly pathogenic strains of influenza. We chose genes from H9N2 influenza for the vaccine because the virus can infect many different animals, including chickens, mice and pigs," said Professor Perez.
"A very important limitation in the current design of flu vaccines is that they are usually species specific. Our approach involves a universal backbone that can be used in several different species, including humans."
More importantly, this live attenuated virus provided effective protection when it was administered to birds before they had hatched. By vaccinating eggs against influenza, we could protect wild bird species as well as domestic chickens against pandemic flu strains, limiting the spread of disease to humans.
"If an emerging strain of bird flu spreads among a broad range of animal species, we should expect major health, economic and ecological consequences," said Professor Perez.
"It is unrealistic to consider preparing different vaccines specifically tailored to different animal species in this situation. An influenza vaccine that could protect different species would save valuable time during a pandemic.".........
ZenMaster

Targeted cell delivery to the cervical spinal cord promising strategy to slow loss of motor neurons in ALSMonday, 20 October 2008
In a disease like ALS - one that is always fatal and that has a long history of research-resistant biology - finding a proof of principle in animal models is significant.
This week, Johns Hopkins researchers report that transplanting a new line of stem cell-like cells into rat models of the disease clearly shifts key signs of neurodegenerative disease in general and ALS in particular - slowing the animals' neuron loss and extending life.
The new work supports the hypothesis that artificially outnumbering unhealthy cells with healthy ones in targeted parts of the spinal cord preserves limb strength and breathing and can increase survival.
An account of the work appears online this week in Nature Neuroscience.
Two parts of the study hold special interest: One is that the target area for the added cells - parts of the cervical spinal cord that control the diaphragm muscles largely responsible for breathing - reaps the most benefit. Forty-seven percent more motor neurons survived there than in untreated model animals. Respiratory failure from diaphragm weakness is the usual cause of death in ALS, also called Lou Gehrig's disease.
"While the added cells, in the long run, didn't save all of the nerves to the diaphragm, they did maintain its nerve's ability to function and stave off death significantly longer," says neuroscientist Nicholas Maragakis, M.D., an associate professor of neurology at Johns Hopkins who led the research team.
"We intentionally targeted the motor neurons in this region," he says, "since we knew that, as in ALS, their death results in respiratory decline."
Also significant is that the transplanted cells, called glial restricted precursors (GRPs), address a well-known flaw in people with ALS and in its animal models. Both humans and models are stunted in their ability to clear away the neurotransmitter glutamate. And excess glutamate - common in ALS – over-stimulates the motor neurons that spark muscle movement, causing death. The event, called excitotoxicity, also occurs in other neurological diseases.
So on a more basic level, the study adds clout to the principle - in live animals - that excitotoxicity is a major bad guy in ALS and that finding more effective ways to avoid or lessen it could help protect the nervous system.
In their research, the team transplanted some 900,000 glial restricted precursors overall to specific sites in the cervical spinal cord of each model rat in early stages of disease. The GRPs the scientists used began life as what is called astrocyte progenitor cells from healthy rat spinal cord tissue. Following transplant, they transformed into mature, healthy astrocytes, found living alongside sick motor neurons.
Astrocytes are the most common cells in the central nervous system. Work at Johns Hopkins and elsewhere has shown their crucial role in keeping the CNS in healthy balance. Not only are the cells studded with transporter molecules that mop up glutamate; they also maintain proper ion levels and nutrient support of nerve cells.
The study showed that at least a third of the added GRPs "took root" after their transplantation. With time, almost 90 percent of the GRPs had differentiated into astrocytes. Unlike the model rats' own astrocytes, the new ones continued to appear healthy. None of the GRPs damaged the spinal cord or formed tumours - a worry with some stem cell therapies.
Transplanting alternate GRPs - those that the team engineered to lack glutamate transporters - offered none of the protective properties.
"Our findings demonstrate that astrocyte replacement, by transplantation, is both possible and useful," Maragakis explains.
"This targeted cell delivery to the cervical spinal cord is a promising strategy to slow that loss of motor neurons in ALS. We hope at some point that these principles will translate to the clinic."
Earlier research by U.S. scientists suggests that, while astrocytes go downhill in ALS, they may not be a primary cause of the disease. The idea is more that they're involved in its progression. Diseased astrocytes, studies show, may make motor neurons more susceptible to death by excitotoxicity.
About ALS:
Amyotrophic lateral sclerosis (ALS) is a motor neuron disorder that affects roughly 30,000 people in the US. It is characterized by a rapid decline in motor neurons, with death from respiratory failure typically occurring from two to five years after diagnosis.
See also on the Web: Robert Packard Center for ALS Research at Johns Hopkins.
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ZenMasterFor more on stem cells and cloning, go to CellNEWS at
http://cellnews-blog.blogspot.com/ and
http://www.geocities.com/giantfideli/index.html

Saturday, 18 October 2008

Salk researchers successfully reprogram keratinocytes attached to a single hair
Saturday, 18 October 2008
The first reports of the successful reprogramming of adult human cells back into so-called induced pluripotent stem (iPS) cells, which by all appearances looked and acted liked embryonic stem cells created a media stir. But the process was woefully inefficient: Only one out of 10,000 cells could be persuaded to turn back the clock.
Now, a team of researchers led by Juan Carlos Izpisúa Belmonte at Salk Institute for Biological Studies, succeeded in boosting the reprogramming efficiency more than 100-fold, while cutting the time it takes in half. In fact, they repeatedly generated iPS cells from the tiny number of keratinocytes attached to a single hair plucked from a human scalp.
Their method not only provides a practical and simple alternative for the generation of patient- and disease-specific stem cells, which had been hampered by the low efficiency of the reprogramming process, but also spares patients invasive procedures to collect suitable starting material, since the process only requires a single human hair.
"Having a very efficient and practical way of generating patient-specific stem cells, which unlike human embryonic stem cells, wouldn't be rejected by the patient's immune system after transplantation brings us a step closer to the clinical application of stem cell therapy," says Belmonte, PhD., a professor in the Gene Expression Laboratory and director of the Center of Regenerative Medicine in Barcelona, Spain.
Keratinocytes form the uppermost layer of skin and produce keratin, a tough protein that is the primary constituent of hair, nails and skin. They originate in the basal layer of the epidermis, from where they move up through the different layers of the epidermis and are eventually shed.
While scientists have successfully reprogrammed different types of mouse cells (fibroblasts, liver and intestinal cells), skin fibroblasts were the only human cell type they had ever tried their hands on. Fibroblasts help make the connective tissue in the body and are the primary cell type in the deeper layers of the skin, where they are responsible for wound healing and the secretion of proteins that form collagen.
For the first set of experiments, first author Trond Aasen, Ph.D., a postdoctoral researcher at the Center of Regenerative Medicine in Barcelona, used viral vectors to slip the genes for the master regulators Oct4, Sox2, as well as Klf4 and c-Myc into keratinocytes cultured from human skin explants. After only 10 days — instead of the more typical three to four weeks — one out of 100 hundred cells grew into a tiny colony with all the markings of a typical human embryonic stem cell colony.
The researchers then successfully prodded what they call keratinocyte-derived iPS cells or KiPS cells to distinguish them from fibroblast-derived iPS cells into becoming all the cell types in the human body, including heart muscle cells and dopamine-producing neurons, which are affected by Parkinson's disease.
Taking advantage of the high efficiency of the keratinocyte reprogramming process, Aasen decided to test whether he could establish KiPS cells from minute amounts of biological samples.
"We plucked a single hair from a co-worker's scalp and cultured the keratinocytes, which are found in the outer root sheet area," recalls Aasen. He then successfully reprogrammed these cells into bona fide KiPS cells.
Just why keratinocytes appear to be much more malleable than other cell types is still an open question.
"We checked a whole rainbow of cells and found keratinocytes to be the easiest to be reprogrammed," says Belmonte.
"It is still not clear exactly why that is and knowing it will be very important for the technology to develop fully," he speculates.
They researchers did find one hint, though. When they compared the expression profiles of genes related to stem cell identity, growth or differentiation between keratinocytes, fibroblasts, human embryonic stem cells (hESC) and KiPS cells, keratinocytes had more in common with hESCs and KiPS cells than with fibroblasts.
Reference:
Efficient and rapid generation of induced pluripotent stem cells from human keratinocytes
Trond Aasen, Angel Raya, Maria J Barrero, Elena Garreta, Antonella Consiglio, Federico Gonzalez, Rita Vassena, Josipa Bili, Vladimir Pekarik, Gustavo Tiscornia, Michael Edel, Stéphanie Boué & Juan Carlos Izpisú Belmonte
Nature Biotechnology, 17 October 2008, doi:10.1038/nbt.1503.........
ZenMaster

A map of where proteins are located in tissues and cells could help scientists understand the molecular basis of diseases
Saturday, 18 October 2008Researchers in Sweden are compiling a remarkable ‘atlas’, the Human Protein Atlas, that pinpoints the location of thousands of individual proteins in the body’s tissues and cells which will give scientists important insights into the function of different proteins and how changes in the distribution of proteins could be reflected in diseases such as cancer. Professor Mathias Uhlén of the Department of Proteomics at the Royal Institute of Technology in Stockholm, who is leading the project, said, “We are trying to map the building blocks of life.”
The project is hugely ambitious, relying on the selective identification and mapping of thousands of proteins, many of whose function is not yet known, and has required the development of a massive infrastructure to enable the proteins to be identified in a realistic period of time.
Uhlén was describing the human protein atlas at the European Science Foundation’s 3rd Functional Genomics Conference in Innsbruck, Austria, on 1-4 October. Functional genomics describes the way in which genes and their products, proteins, interact together in complex networks in living cells. If these interactions are abnormal, diseases can result. The Innsbruck meeting brought together more than 450 scientists from across Europe to discuss recent advances in the role of functional genomics in disease.
The protein atlas team first uses the human genome – the sequence of all the 20000 or so genes in human cells – to encode individual proteins. They then develop ‘antibodies’ – protein molecules that recognise specific targets – against each of these proteins. The antibody that recognises a given protein is then labelled with a marker to render it visible under a microscope and is exposed to samples of different tissues and cells. The antibody binds to the proteins and in this way the location of the protein can be detected.
“To do this systematically requires a lot of automation and robotics,” Uhlén said.
“We have six software engineers writing codes just to keep track on the samples. The project is generating 400 gigabytes of data every day.”
There is a 100-strong team working on the project, with a site due to be set up soon in India, and with antibody-producing sites in Korea and China.
“To get an idea of how far we have come, in our first year we produced one antibody,” said Uhlén.
“This year we are hoping we can make 3000.”
The programme was launched in 2003, and with sufficient funding the first full version of the atlas could be available by 2014, Uhlén believes.
The team has so far mapped the location of around 5000 proteins in human cells and tissues. The researchers are also investigating whether certain common cancers – colon, prostate, lung and breast – have different protein profiles to normal tissue. In this way new ‘biomarkers’ could be identified – molecules which indicate that a tissue or cell is in a diseased state, which could alert doctors to the early stages of a disease.
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ZenMaster

Friday, 17 October 2008

Significant number of exons created from junk DNA seem to play a role in gene regulationFriday, 17 October 2008
For about 15 years, scientists have known that certain "junk" DNA — repetitive DNA segments previously thought to have no function — could evolve into exons, which are the building blocks for protein-coding genes in higher organisms like animals and plants. Now, a University of Iowa study has found evidence that a significant number of exons created from junk DNA seem to play a role in gene regulation.
The findings, which increase understanding of how humans differ from other animals, including non-human primates, appear Oct. 17 in the open-access journal PLoS Genetics.
Nearly half of human DNA consists of repetitive DNA, including transposons, which can "transpose" or move around to different positions within the genome. A type of transposon called retrotransposons are transcribed into RNA and then reintegrated into the genomic DNA. The most common form of retrotransposons in the human genome are Alu elements, which have more than one million copies and occupy approximately 10 percent of the human genome.
"Alu elements are a major source of new exons. Because Alu is a primate-specific retrotransposon, creation of new exons from Alu may contribute to unique traits of primates. We want to better understand this process," said the study's senior author Yi Xing, Ph.D., assistant professor of internal medicine and biomedical engineering, who holds a joint appointment in the University of Iowa Carver College of Medicine and the UI College of Engineering.
To study the impact of Alu-derived exons on human gene expression, the researchers used a high-density exon microarray. The technology has nearly six million probes for monitoring the expression patterns of all human exons. Using data generated by these microarrays, the scientists analyzed 330 Alu-derived exons in 11 human tissues. The team then identified a number of exons with interesting expression and functional characteristics.
"Hundreds of exons in the human genome were created from Alu elements. The whole-genome exon microarray allowed us to quickly identify exons that most likely contribute to the regulation of gene expression and function," said Lan Lin, Ph.D., University of Iowa postdoctoral fellow in internal medicine and the lead author of this study.
Analysis of one human gene, SEPN1, which is known to be involved in a type of muscular dystrophy, along with comparative data from chimpanzee and macaque tissues, suggested that the presence of a muscle-specific Alu-derived exon resulted from a human-specific change that occurred after humans and chimpanzees diverged evolutionarily.
"In this case, this exon is only expressed at a high level in the human muscle but not in any other human or non-human primate tissue, so this implies that the exon plays a functional role in muscle, and this role is human-specific," said Xing, who is also affiliated with University of Iowa Center for Bioinformatics and Computational Biology.
Reference:
Diverse Splicing Patterns of Exonized Alu Elements in Human Tissues
Lan Lin, Shihao Shen, Anne Tye, James J. Cai, Peng Jiang, Beverly L. Davidson, Yi Xing
PLoS Genet 4(10): e1000225. doi:10.1371/journal.pgen.1000225See also:More 'Junk' DNA Proves FunctionalCellNEWS - Tuesday, 04 November 2008.........
ZenMaster

Thursday, 16 October 2008

Chinese Premier Wen Jiabao Sees Science as Key to Development
Thursday, 16 October 2008
During a two-hour meeting with the editor-in-chief of the journal Science, Chinese Premier Wen Jiabao expressed hope for increasing investment in basic research, reducing energy consumption by 4 percent annually as economic gains continue, improving food safety, and leveraging science to help the poor.
Wen's conversation with Bruce Alberts of Science is being published in the journal's 17 October 2008 edition. An editorial written by Wen, plus a news article on science and technology in China, also will appear in a forthcoming issue of Science, which is published by the non-profit American Association for the Advancement of Science (AAAS).
"In recent years, we have continuously increased the level of support" for basic research, Wen told Alberts, describing fundamental scientific investigations as "the wellspring and driving force" of innovation.
"But I think [China's investment in basic research] is still insufficient."
China's Ministry of Science and Technology has reported that 5 percent of the nation's total investment in science is being spent on basic research, according to Alberts, a professor of biochemistry and biophysics at the University of California, San Francisco. By comparison, the U.S. National Science Foundation (NSF) has reported that 17.5 percent of the United States' total investment in science was being spent on basic research in 2007.
However, scientific achievement by Chinese scientists and engineers has turned sharply upward in recent years, based on scholarly journal articles and patents. In addition, Alberts said after returning to Washington, D.C. that he was extremely impressed by the high calibre of students he met at Tsinghua and Peking universities. Among 500,000 young people who took a national university entrance examination in one particular province, for example, only 70 were accepted, according to a student who spoke with Alberts during his trip.
Alberts, visiting Beijing to deliver lectures at the Chinese Academy of Medical Sciences and Tsinghua University, joined Science Asia News Editor Richard Stone for the rare personal meeting with the Chinese Premier and Chen Zhu, China's Minister of Health. Chen was instrumental in arranging the meeting, which was also attended by Science contributing correspondent Hao Xin.
Remarks by Wen — a professional geologist who is in charge of China's government and works closely with President Hu Jintao — "clearly reveal his passion for both science and technology, as well as his recognition of their central importance to society," Alberts said.
For example, when asked about the recent tainted-milk crisis in China, Wen said that both the producers and the government must accept responsibility for preventing foods from being tainted in the future.
"We feel great sorrow about this milk incident," he said.
"I once again solemnly emphasize that it is absolutely impermissible to sacrifice people's lives and health in exchange for temporary economic development."
All foods must meet international standards, and in particular, exported foods must meet the standards of importing countries, Wen said. The Ministry of Health has now been assigned central oversight of food safety in China, he added.
Wen also acknowledged China's challenges in moving toward more environmentally friendly practices, and he promised that the country will continue to make improvements.
"We have established a goal, that is in future development, our [Gross Domestic Product] growth every year must be accompanied by a 4 percent decrease in energy consumption," he said, "and a 2 percent reduction in [chemical oxygen demand] and sulphur dioxide emissions every year."
Noting that China has been an industrial nation only for several decades, he nonetheless added that "we will now begin to shoulder our due responsibilities" for protecting the environment. China's coal production currently exceeds 2.5 billion tons per year.
"This kind of huge consumption of energy, especially non-renewable fossil fuel, will not be sustainable," Wen said.
Alberts congratulated Wen on his country's recent successful space mission. The Science editor-in-chief further proposed that science and science diplomacy can be important tools for helping to ease political tensions between nations because scientists all over the world share common goals to improve human welfare.
Wen agreed. "Exchanges and collaborations between scientists can help promote exchange and co-operations in economic and social realms between countries," he said.
"More scientific language and less diplomatic rhetoric may make this world even better."
Wen applied his scientific training when he was called upon to respond to the tragic 12 May 2008 Wenchuan earthquake. In his conversation with Alberts, Wen described his four priorities for responding to the disaster and helping to prevent earthquake damage in the future. The first priority was to help people, and Wen said that 80,000 were rescued from the earthquake rubble. He described his second priority as improving the monitoring of aftershocks. A third priority was to prevent "quake lakes" from bursting, and Wen said that the Tangjiashan quake lake, containing 300 million cubic meters of water and endangering Mianyang, is being successfully managed. Wen described his fourth priority for disaster recovery as preventing disease in the hardest hit regions.
Alberts' interview with Wen also covered China's "scientific outlook on development." Wen explained that there are several fundamental principles at the heart of China's science-based efforts to improve people's lives and the country's economy.
Specifically, he said that any plan for China's progress should put people first, by seeking to increase material as well as cultural prosperity. In addition, Wen advocated "comprehensive development," which he described as including the integration of economic and political reform, or progress but also traditional Chinese culture. He further said that China's efforts will seek to resolve disparities between rich and poor, and balance development within the agricultural, industry and service sectors of the economy. Finally, he said that China will work toward sustainable development that addresses the inherent challenge of limited resources to support a population of 1.3 billion.
Wen noted that innovation "needs to start with children," who must learn independent thinking and creative problem-solving. He also emphasized that students must cultivate scientific ethics and "uphold the truth, seek truth from facts, be bold in innovation and tolerant of failure." Wen promised to "hold fast to the policy of opening up to the outside world."
Both Wen and Alberts discussed the importance of science education for achieving economic progress, life-changing scientific advances and better understanding between nations.
Coincidentally, the visit between Wen and Alberts took place on the 30th anniversary of the first delegation of AAAS to China, as well as the first anniversary of the opening of Science's Beijing bureau.
The meeting also occurred in tandem with two other key AAAS activities in China. Past AAAS President Peter Raven of the Missouri Botanical Garden had visited China at the same time to deliver the first-ever AAAS-Chinese Academy of Sciences Distinguished Lectureship on Sustainability. Tom Wang, AAAS director for international cooperation who also serves as deputy director for the new AAAS Center for Science Diplomacy, joined Raven on his trip. Catherine Matacic, who runs the EurekAlert! Chinese Web site at AAAS, was in Beijing, too, to coordinate what was believed to be the first China-based press conference related to a Science paper.
The Science press conference in Beijing focused on a study by Chinese scientists who concluded that genetically engineered cotton had effectively reduced populations of cotton bollworms, and also seemed to benefit other crops. The study, by Kongming Wu, Yanhui Lu and Hongqiang Feng of the Chinese Academy of Agricultural Sciences, was the latest example of outstanding China-authored research appearing in Science. Worldwide, Science editors receive some 12,000 submissions each year. Between 7 percent and 8 percent of those submissions, or 840 to 960 articles ultimately are accepted for publication, following rigorous peer review. In 2007, Science published approximately 30 articles with Chinese authors or co-authors, according to Science Deputy Managing Editor Brooks Hanson.
Alberts, president emeritus of the U.S. National Academy of Sciences who served as chair of the National Research Council from 1983 until 2005, has special interests in science education and international scientific cooperation.
"Bruce Alberts joined AAAS and Science after many years of international scientific leadership. His activities have resulted in cooperative relationships with an array of influential scientists, engineers and leaders in other countries," said Alan I. Leshner, chief executive officer of AAAS and executive publisher of Science.
"And one of those connections was able to help facilitate the meeting with the Chinese premier. We also were very fortunate to have an award-winning reporter like Richard Stone on staff who has become very well respected in the Chinese scientific and journalism communities, and thus could help make the right connections for this unique interview."
Since opening the Science Beijing bureau in October 2007, Stone has covered major events such as the devastating earthquake. His reporting has ensured that a steady stream of news and feature stories from China appear in Science. He also has sought to raise Science's profile in China by appearing as a guest commentator on China's English-language TV station, China Central Television (CCTV)-9. Stone described the meeting with Wen at the government leaders' compound in the heart of Beijing, Zhongnanhai, as a thrill and an honor.
"I can't imagine a better way to cap our first year in China," he said.
In 2007, AAAS Chief International Officer Vaughan Turekian and Wang helped to formalize agreements with two of China's leading scientific organizations, outlining plans for collaboration related to publishing, science education, sustainability, science policy, and opportunities for women scientists and engineers. The AAAS agreements with the Chinese Academy of Sciences and the China Association for Science and Technology call for cooperative efforts to translate and disseminate educational materials and high-impact Science papers, among other efforts.
"This meeting demonstrated the seriousness that China's most senior officials place on science and technology as a critical driver to their broader development plans," Turekian said.
"There are only a handful of leaders in the world that would commit this sort of time to meet with a foreign scientist. AAAS and Science were grateful for the opportunity."
About the American Association for the Advancement of Science:
The American Association for the Advancement of Science (AAAS) is the world's largest general scientific society, and publisher of the journal, Science (www.sciencemag.org). AAAS was founded in 1848, and includes some 262 affiliated societies and academies of science, serving 10 million individuals. Science has the largest paid circulation of any peer-reviewed general science journal in the world, with an estimated total readership of one million. The non-profit AAAS (www.aaas.org) is open to all and fulfils its mission to "advance science and serve society" through initiatives in science policy; international programs; science education; and more.
Reference:
China's Scientist Premier
Science 17 October 2008: 362-364, DOI: 10.1126/science.322.5900.362See also:
Chinese premier expounds on "Scientific Outlook on Development"Xinhua - 2008-10-18 .........
ZenMaster

Man's Best Friend Recruited in the Hunt for Disease Genes
Thursday, 16 October 2008
For centuries man has had a uniquely close relationship with dogs – as a working animal, for security and, perhaps most importantly, for companionship. Now, dogs are taking on a new role – they are helping in the hunt for genetic mutations that lead to diseases in humans.
"Dogs get very similar diseases to humans," said Kerstin Lindblad-Toh of Institute of Medical Biochemistry and Microbiology, Uppsala University in Sweden and the Broad Institute of MIT and Harvard, Cambridge, Massachusetts.
"If you ask a dog owner what sort of conditions their pets get, they will say cancer, allergies, eye diseases."
Lindblad-Toh was speaking at the European Science Foundation's 3rd Functional Genomics Conference, held in Innsbruck, Austria, on 1-4 October. Functional genomics describes the way in which genes and their products, proteins, interact together in complex networks in living cells. If these interactions are abnormal, diseases can result. The Innsbruck meeting brought together more than 450 scientists from across Europe to discuss recent advances in the role of functional genomics in disease.
Many canine diseases could share the same genetic basis in humans and dogs, Lindblad-Toh told the conference, and because dogs have been bred into clear isolated populations – the different breeds – it is often easier to detect a genetic flaw that leads to a disease than it is in humans. Once the rogue gene has been found in the dog, it could make it easier look for mutations in the same gene in man.
"For example we have found genetic mutation that results in a condition called day blindness that can affect dachshunds," Lindblad-Toh said. A similar condition can arise in humans, and analysis of the mutated protein in the dog is providing new information about the disease in man. The team is also looking at genes associated with cancer of the blood vessels to which golden retrievers are prone.
A new European consortium has been set up called LUPA, where twenty veterinary schools from 12 countries spread across Europe will work together to collect 10,000 DNA samples from purebred dogs, comparing healthy animals with those affected by similar diseases as human. The analysis of the genome of affected dogs compared to healthy ones of the same breed will lead to the identification of genes implied in the mechanisms of these diseases. The four-year project aims initially to pinpoint genetic markers for dog diseases and help to reduce the high level of inherited disease in purebred dogs. The identification of these genes implied in disease development will help to understand the mechanisms and pathways of the pathology.
For example in Sweden, more than one-third of English Springer Spaniels are diagnosed with mammary tumours, analogous to breast cancers in humans. An increased risk for malignant mammary tumours has been reported also in other breeds, including Cocker Spaniels, German Shepherds and Boxers, suggesting that these breeds may carry genetic risk factors for this type of cancer. If the genes implicated in the disease can be singled out this could provide a new opportunity to improve prevention, diagnosis and treatment of human breast cancer.
"We want to find a lot of risk factors and bring them back to human patients over the next few years," Lindblad-Toh said.
Lupa was the female wolf (Canis lupus) that according to Roman mythology was nurturing the twins Romulus and Remus, founders of Rome.
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Wednesday, 15 October 2008

New Properties of Skin Stem Cells
Wednesday, 15 October 2008
Recent research from the Swedish medical university Karolinska Institutet reveals completely new properties of the skin's stem cells – discoveries that contradict previous findings. The studies, which are published in Nature Genetics, show amongst other things, that hair follicle stem cells can divide actively and transport themselves through the skin tissue.
"The stem cells don't behave at all in the way we'd previously thought, and are found in unexpected places", says Professor Rune Toftgård, one of the scientists at Karolinska Institutet responsible for the study.
"We're now investigating the part played by the stem cells in the wound-healing process and the development of basal cell carcinoma, the most common form of skin cancer."
The stem cells examined by the present study are found in the skin's hair follicles, around which the cells are able to move depending on their stage of growth. The scientists believe that their growth is governed by previously known mechanism called Hedgehog signalling. Mutations in the genes that control this signal system can cause the delayed deactivation of signal transference; the signals thus continue uninhibited, which increases the risk of cancer.
Reference:
Lgr5marks cycling, yet long-lived, hair follicle stem cells
Viljar Jaks, Nick Barker, Maria Kasper, Johan H van Es, Hugo J Snippert, Hans Clevers, Rune Toftgård
Nature Genetics, AOP 12 October 2008, doi 10.1038/ng.239.........
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Impressive advances in our understanding of the genetic basis of disease were outlined at the 3rd ESF Functional Genomics Conference in Innsbruck, AustriaWednesday, 15 October 2008
The mysteries of the human genome are slowly being revealed – but the more we uncover the more complicated the picture becomes. This was one key message to emerge from the European Science Foundation's 3rd Functional Genomics Conference held in Innsbruck, Austria, on 1-4 October.
Functional genomics describes the way in which genes and their products, proteins, interact together in complex networks in living cells. If these interactions are abnormal, diseases can result.
"The human genome is just a string of letters which has to be interpreted so that we can understand the function of the genes," said Mike Taussig of Babraham Bioscience Technologies in Cambridge, UK, who organised the conference, which focused on the role of functional genomics in disease.
More than 450 scientists from across Europe were told of new developments in research ranging from pinpointing genes involved in diabetes and cancer to using the genetic sequences of different breeds of dog to throw light on human diseases.
"What we have tried to do is bring together genome knowledge as it is now, the work which has been done, what it means in functional terms and where it affects our susceptibility to disease," Taussig said.
"Conferences like these are important because we try to cover a broad field – there are so many aspects of genomics that it would be impossible to encompass everything in a single lecture. It is very useful for researchers who want to improve their general view of the field, because when you are immersed in one specialty you often do not appreciate how well connected everything is."
Dr Patrik Kolar, head of the unit for genomics and systems biology in the European Commission's research directorate, said:
"Functional genomics and systems biology is an important and integral part of our health research programme because an understanding of these basic biological processes has huge potential and real applications for understanding disease, and when you understand disease you can design new drugs."
"This kind of conference is one of the things that brings together the European community in functional genomics and I am really happy to see that most of the participants are from collaborative projects funded though our Framework programme," Dr Kolar added.
Professor Mark McCarthy of the University of Oxford in the UK, who is searching for genes involved in type 2 diabetes, illustrated the unexpected complexity of the role of genes in disease. Here, so-called genome-wide scans, which compare the genetic profiles of healthy people with those who have the disease, have so far revealed around 20 individual gene mutations that can be present in people with type 2 diabetes. However, these variants explain only a small proportion of people's overall susceptibility to the condition.
"If you look at the variants we are finding from really large sample sizes, the effects are pretty small," McCarthy told the conference.
"For diabetes, weight and age are still better predictors of risk than the gene profile. So, on the one hand we are happy that we have found more signals that we might have imagined, but on the other hand, we are disappointed because we are explaining so little of the variance. There is much work to be done to turn these association signals into function and mechanism."
Mutations in cancer genes have also turned out to be far more complicated than people might have first suspected. Professor Mike Stratton, head of the Cancer Genome Project at the Wellcome Trust Sanger Institute in Cambridge, UK, led the team that mapped and identified the high-risk breast cancer susceptibility gene BRCA2. His group is searching for particular types of gene mutations in cancer cells, and is revealing new insights into a class of mutation called rearrangement, where one gene breaks and is fused to another. This rearrangement process could result in the creation of a rogue protein that promotes cancer. Until recently, it has been difficult to study rearrangement mutations because technologies have been lacking.
"For many years we have wanted a screen which would allow us to extract rearranged parts of the cancer genome and make a catalogue," Stratton told conference delegates. Techniques have now been developed that are allowing researchers to pinpoint rearrangements and look at them in detail.
"New sequencing technologies are enabling us to look at a much larger number of rearrangements, allowing us to do genome-wide screens to identify fusion genes that could be cancer genes," Stratton said.
"It turns out there is a lot of complexity in these rearrangements that we would not anticipated before westarted." For example it is becoming clear that while there are many more rearrangement mutations than people first thought, the majority of these seem to be effectively harmless, or 'passenger' mutations. The significant mutations are the 'drivers', and these are much more elusive to track down.
Meanwhile Dr Kerstin Lindblad-Toh of Uppsala University in Sweden and the Broad Institute of MIT and Harvard, Cambridge, Massachusetts, is analysing gene mutations in different breeds of dog to throw light on human diseases. Because dogs have been reared as distinct breeds with clear isolated populations, it is often easier to detect a genetic flaw than it is in humans, and dogs are susceptible to many similar diseases that occur in man.
Professor Olli Kallioniemi's team at the Institute for Molecular Medicine in Finland is working on innovative ways to discover the effects of small strands of RNA, called small interfering RNAs (siRNAs), which can 'silence' genes and are showing promise in the fight against diseases such as cancer. The Finnish researchers have developed new high-throughput techniques for testing thousands of different siRNAs on living cells in one go.
"This is a new cell array screening platform which we think has great potential for showing real utility in biological experiments," Kallioniemi told the meeting.
Professor Patrik Brundin of Lund University in Sweden leads a team that is learning how best to repair the brain of people with neurodegenerative disorders such as Parkinson's disease, where a part of the brain called the substantia nigra degenerates, leading to slow movement and tremors. Brundin told the meeting that his university has over the past 20 years transplanted brain tissue into 18 patients with Parkinson's, whose condition improved markedly and remained stable for many years. However, certain unexplained side effects have arisen, including uncontrollable movements.
"Nigral transplants have clearly worked well in select cases, but the technique needs refinement and is difficult to perform in large series of patients," Brundin said. One key issue is a safe and sustainable supply of tissue, and embryonic stem cells could hold promise. However, Brundin warned that many hurdles remain to be overcome.
"Today some people are saying that you can do this with stems cells, but stem cell transplantation to the brain is currently science fiction and should remain so for the moment – there are many challenges before we can do clinical trials."
In all, leading scientists, from Europe and the US, gave twelve key lectures at the meeting. In addition, there were more than 40 symposia, with topics ranging from the role of proteins in ageing to new ways to disable viruses that cause influenza.
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Monday, 13 October 2008

Embryonic Heart Exhibits Impressive Regenerative Capacity
Monday, 13 October 2008
A new study demonstrates that the embryonic mouse heart has an astounding capacity to regenerate, a phenomenon previously observed only in non-mammalian species. The research, published by Cell Press in the October 14th issue of the journal Developmental Cell, describes the previously unrecognized potential of the embryonic heart to replace diseased tissue through compensatory proliferation of healthy cells.
Disorders of the mitochondria, a cell structure required for energy production, are one of the leading causes of fatal early onset cardiomyopathies. To investigate how mutations that interfere with mitochondrial function impact the heart during development, Professor Timothy C. Cox from the University of Washington in Seattle and colleagues from Australia, used a heart-specific knockout approach in mice to inactivate a gene crucial for normal mitochondrial function. Their experimental methods established embryonic female mice with mosaic hearts composed of mixed cell populations: half normal and half "diseased" (lacking the gene). However, surprisingly, at birth the diseased cells represented only about 10% of the cardiac tissue.
Dr. Jörg-Detlef Drenckhahn, now at the Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch said: "Hopefully, our results will lead to new therapies in the future. With the right signals, a heart that has been damaged – for example through infarction – might be stimulated to heal itself."
For the heart to be able to beat, it needs energy. If the energy production in the heart cells is disturbed, then the embryo will actually die of heart dysfunction. But if only a portion of the cells is affected, this is not the case: With the aid of the remaining healthy cells, the embryo manages to regenerate the heart.
The scientists switched off a gene (Holocytochrome C synthase, abbreviated Hccs) in the developing hearts of mice – a gene that is essential for energy production. Results showed that the embryos died when all cells in the heart were affected by the defective energy production. However, the animals that still had some healthy myocardial cells survived, and at the time of birth, they had a heart that was fully able to function.
The gene Hccs is located on one of the sex chromosomes, the X chromosome. In contrast to male animals who have only one X chromosome, females have two X chromosomes. Some of the altered female mice have an X chromosome with the defective Hccs gene and one with the intact Hccs gene. However, in the cells of the female animals, only one X chromosome is active. Depending on which one is expressed, either healthy or diseased heart cells develop.
"At this point in time, the heart of the mice is like a mosaic," Dr. Drenckhahn said. "Half of the cells are healthy, the other half not."
Up until birth, the foetal heart manages to improve the ratio of healthy cells to defective cells from the original 50:50 ratio. The defective cells then only comprise ten percent of the entire heart volume. That is possible because the healthy myocardial cells divide much more frequently than the defective cells. Their percentage in the heart increases so that, at the time of birth, the ratio is large enough to allow the heart of the newborn mouse to beat normally.
"But even for a while after birth, the heart is capable of compensatory growth of healthy cardiac cells," Dr. Drenckhahn explained.
Later the heart loses this ability. Thus, after approximately one year, some of the mice (13 percent) died of myocardial insufficiency and almost half developed arrhythmia. Why only some of the mice develop heart problems is still unclear. This may indicate a hitherto unsuspected embryological origin for early onset cardiac disease in humans. The scientists, therefore, want to inactivate the gene in adult mice as well in order to investigate its influence.
"Our findings reveal an impressive regenerative capacity of the foetal heart that can compensate for an effective loss of half of the cardiac tissue," concludes Professor Cox.
"To the best of our knowledge, this represents the first in vivo demonstration of selection against diseased tissue during embryonic heart development."
The work also suggests that some cell populations within the heart are better able to regenerate than others and that those others are likely to be the source of later pathology. Furthermore, they want to identify the embryonic/foetal signal substances that stimulate healthy cells to proliferate and inhibit diseased cells. The scientists hope that, in the future, these signal substances may help stimulate the body's own repair mechanisms of the heart, for example after a heart attack or in the case of heart insufficiency.
Reference:
Compensatory growth of healthy cardiac cells in the presence of diseased cells restores tissue homeostasis during heart development
Jörg-Detlef Drenckhahn1, Quenten P. Schwarz, Stephen Gray, Adrienne Laskowski, Helen Kiriazis, Ziqiu Ming, Richard P. Harvey, Xiao-Jun Du, David R. Thorburn and Timothy C. Cox
Developmental Cell, 15, 521-533, October 14, 2008 See also:
Embryonic Stem Cells Repair Congenital Heart DefectCellNEWS - Friday, 12 September 2008 .........
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UN International Bioethics Committee to debate the issue once moreMonday, 13 October 2008
The permissibility of therapeutic cloning will be the focus of a United Nations ethics panel later this month when it considers whether a non-binding General Assembly declaration calling on Member States to ban all forms of human cloning should be reassessed in light of scientific, ethical, social, political and legal advances.
In 2005 a minority of the General Assembly declared all human cloning incompatible with human dignity and protection of life, voting 84 in favour, 34 against, 37 abstaining and 36 absent, after a decade of work on reproductive cloning by the International Bioethics Committee (IBC) of the UN Educational, Scientific and Cultural Organization (UNESCO).
Now the IBC will debate the issue once more at a two-day meeting at UNESCO headquarters in Paris beginning 28 October, noting that some people, mainly scientists, are urging a different approach to therapeutic cloning.
“Recent technological developments and new prospects for the use of stem cells in the therapy of human diseases have once again raised the issue of adequacy of international regulations governing this research,” an IBC working group set up at the request of UNESCO Director-General Koïchiro Matsuura said in a report in September.
The report noted that the main point of controversy in the 2005 Declaration was the question of linking the issues of reproductive and non-reproductive cloning, which was not agreeable to many States who abstained or voted against.
The Group calls for human reproductive cloning to be banned at the international level by a legally binding convention, while guidelines for regulating human embryo and stem cell research in countries where it is legal should be developed at the international level.
An Observatory Group could be established to new ethical, legal, social, political and scientific developments, and UNESCO should develop specific strategies and materials to promote international dialogue on this topic.
The other focus of this month’s meeting is the principle of social responsibility as set forth in the Universal Declaration of Bioethics and Human Rights of 2005, including article 14, which states that “the promotion of health and social development for their people is a central purpose of governments that all sectors of society share.”
An IBC working group stressed that this implies that health should be one of the most important purposes of governments, while promoting health and social responsibility is an obligation shared by all societal actors, private and public.
Source: UN News Service
See also:
Minority of UN Vote against Human Cloning CellNEWS - Tuesday, 08 March 2005 .........
ZenMaster

Saturday, 11 October 2008

Giant Panda Genome Sequence CompletedSaturday, 11 October 2008Chinese scientists have completed sequencing the genome of giant pandas, Xinhua news agency reported on Saturday. They hope the new information will give them a better biological understanding of why pandas eat bamboo, have black circles around their eyes and produce few offspring.
"By sequencing the giant panda genome we've laid the genetic and biological foundation for us to gain a deeper understanding of the peculiar species," said Dr. Wang Jun, a scientist with the Beijing Genomics Institute's Shenzhen branch (BGI Shenzhen), a core participant in the project.
The International Giant Panda Genome Project only started in March 2008 with scientists from China, Britain, the United States, Denmark and Canada. The Beijing Genomics Institute, Shenzhen (BGI-SZ), initiated it.
The giant panda genome is approximately the same size as the human genome, and is thought to have 20,000-30,000 genes. Taxonomy and genetic studies indicate that the giant panda is most closely related to bears, not to raccoons as was once considered, given their unique physical characteristics.
So far, scientists learned, through drawing and assembling the genome sequence that giant pandas are akin to dogs and human beings but are very different from mice. They also discovered more supporting evidence that giant pandas might be a subspecies of black bears.
Giant pandas are among the world's most endangered animals due to their shrinking habitat. It was one reason why scientists decided to sequence its genome.
"It will help genetically explain why giant pandas have poor reproductive abilities, so that scientists can help them deliver more cubs," Wang said.
Wang said knowledge of the genome could also help efforts to control disease among pandas.
Scientists for the genome sequencing chose a three-year-old female panda, named Jing Jing, from the Chengdu Research Base of Giant Panda breeding in southwest China’s Sichuan Province. Jing Jing was also the prototype of one of the five mascots of the Beijing Olympics.
There are about 1,590 pandas living in China's wild, mostly in Sichuan and the north-western provinces of Shaanxi and Gansu. In 2007, there were 239 captive-bred giant pandas in China.
Yang Huanming, another scientist at BGI Shenzhen, said his colleagues would work on mapping out a more detailed genome sequence of the panda by the end of this year.
Chinese scientists have made big improvements in gene studies and genome sequencing in the past few years through their own efforts and participation in a series of international projects. They have contributed to the genome sequencing of a rice paddy, silkworm, hen and pig. In October last year, they finished sequencing the first Han Chinese genome.
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ZenMaster

Friday, 10 October 2008

Yamanaka eliminates viral vector in stem cell reprogramming, improving safety
Friday, 10 October 2008
Shinya Yamanaka MD, PhD, of Kyoto University and the Gladstone Institutes of Cardiovascular Disease (GICD) has taken another step forward in improving the possibilities for the practical application of induced pluripotent stem (iPS) cell technology.
Previously, Dr. Yamanaka had shown that adult cells can be reprogrammed to become embryonic stem cell–like using a cancer-causing oncogene as one of the four genes required to reprogram the cells, and a virus to transfer the genes into the cells. In the last year, Dr. Yamanaka and other labs showed that the oncogene, c-Myc, is not needed. However the use of viruses that integrate into the genome prohibit use of iPS cells for regenerative medicine because of safety concerns: its integration into the cell's genome might activate or inactivate critical host genes.
Now Dr. Yamanaka's laboratory in Kyoto has eliminated the need for the virus. In a report published this week in Science, they showed that the critical genes can be effectively introduced without using a virus. The ability to reprogram adult cells into iPS cells without viral integration into the genome also lays to rest concerns that the reprogramming event might be dependent upon viral integration into specific genomic loci that could mediate the genetic switch.
"The iPS field and stem cell research in general is progressing rapidly," said GICD Director Deepak Srivastava, MD.
"But, as Shinya has shown, each step forward reveals a new set of challenges."
Dr. Yamanaka's team began this series of experiments by replacing the retrovirus with an adenoviral vector. While transfections with the genes on separate vectors didn't work, they did work when the genes were arranged in a specific order on a single vector. The same arrangement worked when the genes were incorporated into a plasmid.
To determine if the plasmid-mediated reprogrammed cells were pluripotent, the scientists transplanted the cells under the skin of immunocompromised mice. The resulting tumours contained a wide variety of cell types from all three germ layers. iPS cells injected into embryos resulted in chimeric mice with the injected cells contributing to almost all cell types.
Still, other problems remain to be solved. The efficiency of the gene transfer with the plasmid was lower than with the retrovirus. Nevertheless, this significant step moves us closer to realizing the promise of stem cells in the understanding and eventual cure of diseases.
About the Gladstone Institutes
The J. David Gladstone Institutes, affiliated with the University of California, San Francisco (UCSF), is dedicated to the health and welfare of humankind through research into the causes and prevention of some of the world's most devastating diseases. Gladstone is comprised of the Gladstone Institute of Cardiovascular Disease, the Gladstone Institute of Virology and Immunology and the Gladstone Institute of Neurological Disease.
Reference:
Generation of Mouse Induced Pluripotent Stem Cells without Viral Vectors
Okita K, Nakagawa M, Hyenjong H, Ichisada T, Yamanaka S.
Science, Published Online October 9, 2008, DOI: 10.1126/science.1164270.........
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Provides the first complete developmental blueprint of a vertebrate
Thursday, 09 October 2008
Researchers at the European Molecular Biology Laboratory (EMBL) have generated a digital zebrafish embryo - the first complete developmental blueprint of a vertebrate. With a newly developed microscope scientists could for the first time track all cells for the first 24 hours in the life of a zebrafish. The data was reconstructed into a three-dimensional, digital representation of the embryo. The study, published in the current online issue of Science, grants many new insights into embryonic development. Movies of the digital embryo and the underlying database of millions of cell positions, divisions and tracks will be made publicly available to provide a novel resource for research and scientific training.
To get from one cell to a complex organism, cells have to divide, travel around the body and arrange intricate shapes and specialized tissues. The best way to understand these dynamic processes is to look at what happens in the first few hours of life in every part of an embryo. While this is possible with invertebrates with a few hundred cells, like worms for example, it has so far been impossible to achieve for vertebrates.

"Imagine following all inhabitants of a town over the course of one day using a telescope in space. This comes close to tracking the 10 thousands of cells that make up a vertebrate embryo – only that the cells move in three dimensions," says Philipp Keller. Together with Annette Schmidt he carried out the research in the labs of Jochen Wittbrodt and Ernst Stelzer at EMBL.
Two newly developed technologies were key to the scientists' interdisciplinary approach to tracking a living zebrafish embryo from the single cell stage to 20,000 cells: a Digital Scanned Laser Light Sheet Microscope, that scans a living organism with a sheet of light along many different directions so that the computer can assemble a complete 3D image, and a large-scale computing pipeline operated at the Karlsruhe Institute of Technology.
Zebrafish is a widely used model organism that shares many features with higher vertebrates. Taking more than 400,000 images per embryo the interdisciplinary team generated terabytes of data on cell positions, movements and divisions that were reassembled into a digital 3D representation of the complete developing embryo.
"The digital embryo is like Google EarthTM for embryonic development. It gives an overview of everything that happens in the first 24 hours and allows you to zoom in on all cellular and even sub-cellular details," says Jochen Wittbrodt, who has recently moved from EMBL to the University of Heidelberg and the Karlsruhe Institute of Technology.
New insights provided by the digital embryo include: fundamental cell movements that later on form the heart and other organs are different than previously thought and the position of the head-tail body axes of the zebrafish is induced early on by signals deposited in the egg by the mother.
The new microscopy technology is also applicable to mice, chickens and frogs. A comparison of digital embryos of these species is likely to provide crucial insights into basic developmental principles and their conservation during evolution.

Thursday, 9 October 2008

Neurons and Muscle Cells Need Stabilizing Force for Effective CommunicationThursday, 09 October 2008
You cannot raise a finger without your brain directing muscle cells, and scientists have figured out another reason that usually works so well.
A neuron sends a message, or neurotransmitter, to the muscle cell to tell it what to do. To get the message, the receiving cell must have a receptor. Oddly, the unstable protein rapsyn is responsible for anchoring the receptor so it is properly positioned to catch the message.
Medical College of Georgia scientists have found what keeps rapsyn in proper conformation.
It is a heat shock protein, one of a large family of molecular chaperones that make sure proteins get where they are needed and do what they should, says Dr. Lin Mei, chief of developmental neurobiology at MCG and Georgia Research Alliance Eminent Scholar in Neuroscience.
Hsp90β helps stabilize rapsyn so receptors can get and stay where needed, according to research published in the Oct. 9 issue of Neuron. Dr. Mei suspects that other hsp siblings have a similar caretaker role in neuron-to-neuron communication in the brain.
Scientists knew rapsyn's role in getting neuromuscular receptors to aggregate and stay where needed, but they didn't know what stabilized it.
"It makes you wonder how to control this naughty boy which is very important," says Dr. Mei, the study's corresponding author.
They found hsp90β wherever rapsyn clustered in muscle cells. When they disrupted its activity or expression, they realized hsp90β's stabilizing role in forming and maintaining receptor clusters, says Dr. Shiwen Luo, postdoctoral fellow in Dr. Mei's lab and the study's first author. Rapsyn and the receptor apparently interact, and then hsp90β comes along to help stabilize the relationship.
Rapsyn mutations have been implicated in muscular dystrophies including congenital myasthenia gravis. MCG researchers are looking now to see if a mutated rapsyn still interacts with hsp90β.
They used a type of acetylcholine nicotinic receptor at the neuromuscular junction as a model for their studies of brain development and communication. The junction is 1,000 times larger than connections, or synapses, between two neurons but structurally similar. Fundamentals include presynaptic terminals that release neurotransmitters picked up by receptors on the postsynaptic side. Terminals and receptors must be lined up well, whether it's a muscle cell or neuron getting the message.
"In central nervous system synapses and at the neuromuscular junction, receptors have to be concentrated at the right spot to receive the neurotransmitter released," says Dr. Mei. If receptors are in the wrong place, the message can be weak or even lost.
At the neuromuscular juncture, communication is usually straightforward, with primarily one neurotransmitter and one principal receptor.
"Whenever you tell a muscle to move, it moves. If you want your muscles to think, you wouldn't be able to pick up a pin," says Dr. Mei. In the brain, where neurons have thousands of synapses, it is more of a negotiation.
"Signals have to be integrated in the neuron for it to decide what to do.".........
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